Synthesis of novel multidentate carbohydrate-triazole ligands

Article abstract of DOI:10.1016/j.tetlet.2008.01.081

Cu(I)-catalyzed 1,3-dipolar cycloaddition (click reaction) of 1 mol equiv of N,N′-di-prop-2-ynyl-phthalamide (1a), N,N′-di-prop-2-ynyl-isophthalamide (1b), and pyridine-2,6-dicarboxylic acid bis-prop-2-ynylamide (1c), respectively with 2 mol equiv of 2,3,

Full text of DOI:10.1016/j.tetlet.2008.01.081

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2166–2169
Synthesis of novel multidentate carbohydrate-triazole ligands
Thomas Ziegler *, Catrin Hermann
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany
Received 10 August 2007; revised 15 January 2008; accepted 16 January 2008
Available online 20 January 2008
Abstract
Cu(I)-catalyzed 1,3-dipolar cycloaddition (click reaction) of 1 mol equiv of N,N0-di-prop-2-ynyl-phthalamide (1a), N,N0-di-prop-2-
ynyl-isophthalamide (1b), and pyridine-2,6-dicarboxylic acid bis-prop-2-ynylamide (1c), respectively with 2 mol equiv of 2,3,4,6-tetra-
O-acetyl-b-D-glucopyranosyl azide (2a), 2-azidoethyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (2b), and 2-azidoethyl 2,3,4,6-tetra-O-
acetyl-a-D-mannopyranoside (2c), respectively, afforded the corresponding bis-cycloadducts 3–5, containing two 1,2,3-triazole moieties
each, in 38–76% yield. Reaction of 1 mol equiv of 2c with 1 mol equiv of 1c under otherwise identical conditions gave the mono-cyclo-
adduct 6, containing one 1,2,3-triazole and one 2-propynylamide moiety, in 77% yield. Reaction of 6 with 2a afforded 7, containing two
different sugar moieties, in 67% yield.
Ó 2008 Elsevier Ltd. All rights reserved.
Multivalent carbohydrate–protein interactions play fun-
damental roles in many biological processes like infection
mechanisms, immunological processes, inflammation, sig-
nal transduction and cell differentiation. The majority of
biogenic proteins is also glycosylated, and the glycosyl part
of these proteins influences their biological activity. How-
ever, the molecular basis for such processes is still
unclear.1,2 This is especially true for carbohydrates and
complex saccharides where cluster effects and the topo-
graphic arrangement of the sugar moieties are crucial
factors, which reign over the magnitude of the binding of
a sugar to a receptor or the specific interaction of saccha-
rides with proteins. Often, carbohydrate–metal complexes
are also involved in the specific binding of sugars to pro-
teins.3 Therefore, synthetic carbohydrate ligands are useful
tools to study their complex interactions with proteins on a
molecular level. Especially, carbohydrate–metal complexes
had been recently shown to provide for deeper insight into
carbohydrate–protein interactions4–8 or for analytical tools
valuable for studying such interactions in greater detail.9,10
Here, we describe a flexible and straightforward synthe-
sis of novel multidentate carbohydrate ligands via Cu(I)-
catalyzed 1,3-dipolar cycloaddition11–23 of glycosyl azides
and azidoethyl glycosides with bivalent 2-propynyl deriva-
tives. Thus we obtained 1,2,3-triazole-linked multidentate
carbohydrate ligands that are aimed at further studying
the topography of their complexes with metal ions which,
in turn, is thought to tune the binding properties of the
sugar moieties to proteins (i.e., switchable carbohydrate
recognition). We chose the 2-propynyl diamides 1a–c as
the alkynyl components for the 1,3-dipolar cycloaddition
of glycosyl azides and 2-azidoethyl glycosides. They were
prepared from the corresponding acid dichlorides and 2-
propynyl amine (THF, 0–20 °C, 3 h) in 50–84% yield.24
Scheme 1 and Table 1 summarize the 1,3-dipolar cyclo-
additions of 1a–c with 2 mol equiv each of 2,3,4,6-tetra-
O-acetyl-b-D-glucopyranosyl azide (2a),25 2-azidoethyl
2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (2b),17 and 2-
azidoethyl
2,3,4,6-tetra-O-acetyl-a-D-mannopyranoside
(2c),26, respectively.
Under catalysis with (EtO)3PCuI,27 all double click-
reactions proceed smoothly at rt without the need of ultra-
sound irradiation. Careful inspection of the TLCs drawn in
the course of the reactions revealed that the two cycloaddi-
tion steps proceed at different velocities. The first addition
*
Corresponding author. Tel.: +49 70 71 29 78763; fax: +49 70 71 29
73035.
E-mail address: thomas.ziegler@uni-tuebingen.de (T. Ziegler).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.081

T. Ziegler, C. Hermann / Tetrahedron Letters 49 (2008) 2166–2169
2167
R-N3
OAc
NH
NH
NH
N
N
R
N
N
N
N
R-N3
i
O
O
O
O
O
AcO
AcO
N3
R
OAc
NH
2a
2b
1a
3-5a
OAc
O
AcO
AcO
O
N
O
O
N
N3
H
N
O
O
H
N
OAc
R
N
R-N3
i
X
X
AcO
AcO
AcO
OAc
O
N
H
N
H
R
N
N
N
O
2c
3-5b X = CH
3-5c X = N
N3
1b X = CH
1c X = N
Scheme 1. Reagents and conditions: (i): 0.1 equiv (EtO)3PCuI, 3 equiv DIPEA, DME, 1–18 h rt, 38–79%.28
Table 1
pressure, filtration through a short layer of silica gel, and
drying in vacuo as exemplified for ligands 3b, 4a,b, and
5a in Scheme 3.29
Click reaction of bis-2-propynyl derivatives 1 with azides 228
1
R–N3
Conditions
3–5
Yield (%)
Preliminary results for the complexation of the ligands
3–5, and 7 with ZnCl2 show that complex formation does
take place at the amide carbonyl group and N-3 of the tri-
azole groups. Similar coordination complexes, where N-3
of a triazole moiety of the ligand is involved, have been
reported recently.30,31 For example, treatment of a solution
of 4b in acetone–methanol (1:1) with 1 mol equiv of ZnCl2
for 72 h, followed by slow evaporation of the solvents
furnishes an amorphous white solid, the spectral properties
of which are in accordance with structure 8a (Scheme 4).32
Most significantly, the specific rotation decreases from
ꢀ13.4 for 4b to ꢀ15.1° for 8a, and the proton NMR signals
for the NH group and the CH group of the triazole moiety
are shifted downfield upon complexation. Similarly, the
carbon NMR signals for the carbonyl group of the iso-
phthalamide moiety, the NCH2 group, and C-4 of the
1,2,3-triazole moiety show an upfield shift of 1.1–2.5 ppm
while the methylene groups of the sugar and the triazole
moieties are downfield shifted by 1.1 and 1.9 ppm, respec-
tively. Furthermore, MS data32 and NMR titration exper-
iments show that a 1:1 complex between 4b and ZnCl2 is
formed. Similar observations were made for the ZnCl2
complex 8b obtained from ligand 5c. However, no crystals
suitable for X-ray could be obtained from any of the com-
plexes so far. Thus, structures 8a and 8b are preliminary.
1a
1b
1c
1a
1b
1c
1a
1b
1c
2a
2a
2a
2b
2b
2b
2c
2c
2c
18 h, 20 °C
18 h, 20 °C
18 h, 20 °C
12 h, 20 °C
14 h, 20 °C
1 h, 20 °C
15 h, 20 °C
15 h, 20 °C
2 h, 20 °C
3a
3b
3c
4a
4b
4c
5a
5b
5c
68
72
38
79
76
76
69
71
76
of 1 mol equiv azide 2 to 1 proceeds faster while the addi-
tion of the 2 mol equiv azide 2 proceeds significantly
slower.
The different velocities of the two cycloaddition steps
also allow for the preparation of ligands bearing two differ-
ent sugar moieties. When dipolarophile 1b is reacted with
only 1 mol equiv of glucoside 2b, the mono adduct 6 is
obtained in 77% yield. Next, crude 6 was treated with
mannoside 2c to afford the mixed ligand 7 in 67% yield
(Scheme 2).
All ligands 3–5, and 7 can easily be deacetylated by
treatment of a methanolic solution of the ligands with
ammonia in MeOH for 16 h at rt, or by a classical Zemplen
deacetylation with a catalytic amount of NaOMe in MeOH
for 30 min at rt, followed by concentration under reduced
´
AcO
AcO
AcO
OAc
O
i
1b + 2b
N
O
H
N
O
N
N
H
N
O
N
N
2c
OAc
O
OAc
ii
AcO
AcO
O
AcO
AcO
O
N
H
O
N
H
N
N
O
AcO
N
O
AcO
N
6
7
Scheme 2. Reagents and conditions: (i): 1 equiv 1b, 1 equiv 2b, 0.1 equiv (EtO)3PCuI, 3 equiv DIPEA, DME, 1 h, 0 °C, 12 h, rt, 77% 6; (ii): 1 equiv 6,
1 equiv 2c, 0.1 equiv (EtO)3PCuI, 3 equiv DIPEA, DME, 12 h, rt, 67% 7.

2168
T. Ziegler, C. Hermann / Tetrahedron Letters 49 (2008) 2166–2169
OH
O
OH
O
N
O
N
HO
HO
H
N
HO
HO
N
N
NH
NH
O
O
N
N
OH
i
ii
N
N
OH
OH
O
N
N
O
O
3b
4a
OH
O
HO
HO
HO
HO
N
H
OH
N
N
O
N
OH
OH
O
HO
OH
HO
HO
N
N
O
O
O
O
O
N
HO
HO
HN
OH
i
ii
4b
5a
O
NH
NH
OH
O
N
N
HO
HO
HO
OH
O
N
N
N
N
O
O
HO
HO
N
H
N
OH
N
O
Scheme 3. Reagents and conditions: (i): 7 M NH3 in MeOH, 16 h, rt, 99% from 3b, 72% from 4b; (ii): cat. NaOMe in MeOH, 30 min, rt, 96% from 4a, 98%
from 5a.
OAc
NH
NH
O
AcO
AcO
O
O
N
N
N
N
OAc
O
O
N
i
Cl
Zn
4b + ZnCl2
Cl
N
OAc
O
AcO
AcO
OAc
8a
AcO
AcO
AcO
OAc
O
NH
N
O
i
N
5c + ZnCl2
N
O
N
OAc
O
AcO
AcO
AcO
Cl
Cl Zn
N
N
O
N
O
NH
8b
Scheme 4. Reagents and conditions: (i): 1 mol equiv 4b or 5c, 2 mol equiv ZnCl2, acetone–MeOH 1:3, 72 h, rt, 100% 8a,b.
5. Sakai, S.; Shigemasa, Y.; Sasaki, T. Tetrahedron Lett. 1997, 38, 8145–
Further investigations for the complex-forming proper-
ties of the multidentate ligands 3–5 and 7 are underway.
8148.
6. Roy, R.; Kim, J. M. Tetrahedron 2003, 59, 3881–3893.
7. Orlandi, S.; Annuntiata, R.; Banaglia, M.; Cozzi, F.; Manzoni, L.
Acknowledgments
Tetrahedron 2005, 61, 10048–10060.
8. Bourne, Y.; van Tilbeurgh, H.; Cambillau, C. Curr. Opin. Struct. Biol.
We thank Professor K. Albert and his group for measur-
ing the NMR spectra, Professor K. P. Zeller and his crew
for performing the mass spectrometry, and P. Kruger for
¨
performing the elemental analyses. This work was finan-
cially supported by the State of Baden-Wurttemberg and
¨
1993, 3, 681–686.
9. Hasegawa, T.; Yonemura, T.; Matsuura, K.; Kobayashi, K. Tetra-
hedron Lett. 2001, 42, 3989–3992.
10. Kojima, S.; Hasegawa, T.; Yonemura, T.; Sasaki, K.; Yamamoto, K.;
Makimura, Y.; Takahashi, T.; Suzuki, T.; Suzuki, Y.; Kobayashi, K.
Chem. Commun. 2003, 1250–1251.
the Fonds der Chemischen Industrie.
11. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596–2599.
References and notes
12. Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057–3064.
1. Laederach, A.; Reilly, P. J. Proteins: Struct. Funct. Bioinform. 2005,
60, 591–597.
2. Lutzen, A.; Wittmann, V. In Highlights in Bioorganic Chemistry;
Schmuck, C., Wennemers, H., Eds.; Wiley-VCH, 2004; pp 119–123.
3. Lectins and Glycobiology; Gabius, H.-J., Gabius, S., Eds.; Springer,
1993.
13. Joosten, J. A. F.; Tholen, N. T. H.; El Maate, F. A.; Brouwer, A. J.;
van Esse, G. W.; Rijkers, D. T. S.; Liskamp, R. M. J.; Pieters, R. J.
Eur. J. Org. Chem. 2005, 3182–3185.
14. Chittaboina, S.; Xie, F.; Wang, Q. Tetrahedron Lett. 2005, 46, 2331–
2336.
15. Chen, Q.; Yang, F.; Du, Y. Carbohydr. Res. 2005, 340, 2476–
2482.
4. Sakai, S.; Sasaki, T. J. Am. Chem. Soc. 1994, 116, 1587–1588.

T. Ziegler, C. Hermann / Tetrahedron Letters 49 (2008) 2166–2169
2169
20
16. Gupta, S. S.; Kuzelka, J.; Singh, P.; Lewis, W. G.; Manchester, M.;
Finn, M. G. Bioconjugate Chem. 2005, 16, 1572–1579.
17. Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem.
2006, 51–68.
18. Bouillon, C.; Meyer, A.; Vidal, S.; Jochum, A.; Chevolot, Y.; Cloarec,
J.-P.; Praly, J.-P.; Vasseur, J.-J.; Morvan, F. J. Org. Chem. 2006, 71,
4700–4702.
19. Tejler, J.; Tullberg, E.; Frejd, T.; Leffler, H.; Nilsson, U. J. Carbohydr.
Res. 2006, 341, 1353–1362.
20. Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9, 1–4.
21. Pukin, A. V.; Branderhorst, H. M.; Sisu, C.; Weijers, C. A. G. M.;
Gilbert, M.; Liskamp, R. M. J.; Visser, G. M.; Zuilhof, H.; Pieters, R.
J. ChemBioChem 2007, 8, 1500–1503.
(C-3), 67.5 (C-4), 61.9 (C-6), 34.8 (NCH2). Compound 3c: ½aꢁD ꢀ41.4
(c 1.0, DMSO), EI-MS: 988.3 [MH]+, 1H NMR (significant signals,
400 MHz, DMSO-d6) d 9.29 (t, 2H, NH), 8.18 (s, 2H, Htriazole), 6.22
(d, 2H, H-1, J = 9.1 Hz); 13C NMR (significant signals, 100 MHz,
DMSO-d6) d 164.0 (CONH), 146.0 ðCtqriazoleÞ, 122.5 (CHtriazole), 85.6
(C-1), 75.1 (C-5), 73.2 (C-2), 71.1 (C-3), 68.5 (C-4), 62.5 (C-6), 35.1
20
(NCH2). Compound 4a: ½aꢁD ꢀ14.0 (c 1.0, CHCl3), EI-MS: 1075.3
[MH]+, 1H NMR (significant signals, 400 MHz, acetone-d6) d 8.18 (t,
2H, NH), 7.94 (s, 2H, Htriazole), 4.79 (d, 2H, H-1, J = 8.1 Hz); 13C
NMR (significant signals, 100 MHz, acetone-d6) d 169.4 (CONH),
136.7 ðCtqriazoleÞ, 124.1 (CHtriazole), 101.1 (C-1), 73.3 (C-3), 72.4 (C-5),
71.8 (C-2), 69.3 (OCH2), 68.7 (C-4), 62.6 (C-6), 50.4 (OCH2CH2), 36.3
20
(NCH2). Compound 4c: ½aꢁD ꢀ14.2 (c 1.0, CHCl3), EI-MS: 1076.2
22. Dedola, S.; Nepogodiev, S. A.; Field, R. A. Org. Biomol. Chem. 2007,
5, 1006–1017.
[MH]+, 1H NMR (significant signals, 400 MHz, acetone-d6) d 9.26 (t,
2H, NH), 7.81 (s, 2H, Htriazole), 4.77 (d, 2H, H-1, J = 8.1 Hz); 13C
NMR (significant signals, 100 MHz, acetone-d6) d 164.0 (CONH),
145.6 ðCtqriazoleÞ, 124.1 (CHtriazole), 101.1 (C-1), 73.2 (C-3), 72.4 (C-5),
71.8 (C-2), 69.3 (OCH2), 68.7 (C-4), 62.6 (C-6), 50.5 (OCH2CH2), 35.4
23. Angell, Y. L.; Burgess, K. Chem. Soc. Rev. 2007, 36, 1674–1689.
24. Compound 1a: 84% yield, mp 177 °C (EtOH), 1H NMR (400 MHz,
CDCl3) d 7.59–7.45 (m, 4H, HPh), 6.92 (br s, 2H, NH), 4.17 (dd, 4H,
CH2), 2.25 (t, 2H, CH); Compound 1b: 80% yield, mp 131–132 °C
(EtOH), 1H NMR (400 MHz, DMSO-d6) d 9.05 (t, 2H, NH), 8.33 (s,
1H, HPh), 7.98 (dd, 2H, HPh), 7.57 (t, 1H, HPh), 4.07 (dd, 4H, CH2),
3.14 (t, 2H, CH). Compound 1c: 50% yield, mp 192 °C (EtOH), 1H
NMR (400 MHz, DMSO-d6) d 9.73 (t, 2H, NH), 8.19 (m, 3H, HPh),
4.19 (dd, 4H, CH2), 3.20 (t, 2H, CH); all compounds gave satisfactory
elemental analyses.
25. Subramaniam, S.; Neira, S. Carbohydr. Res. 1992, 223, 169–
185.
26. Chernyak, A. Y.; Sharma, G. V. M.; Kononov, L. O.; Krishna, P. R.;
Levinsky, A. B.; Kochetkov, N. K.; Rao, A. Carbohydr. Res. 1992,
223, 303–310.
20
(NCH2). Compound 5a: ½aꢁD +25.5 (c 1.0, CHCl3), EI-MS: 1075.3
[MH]+, 1H NMR (significant signals, 400 MHz, acetone-d6) d 8.09 (t,
2H, NH), 8.05 (s, 2H, Htriazole), 4.88 (s, 2H, H-1); 13C NMR
(significant signals, 100 MHz, acetone-d6) d 169.5 (CONH), 146.1
ðCtqriazoleÞ, 124.2 (CHtriazole), 98.1 (C-1), 69.9 (2C, C-3, C-5), 69.5 (C-2),
67.0 (OCH2), 66.4 (C-4), 62.9 (C-6), 50.2 (OCH2CH2), 36.3 (NCH2).
20
Compound 5b: ½aꢁD +31.5 (c 1.0, CHCl3), EI-MS: 1075.2 [MH]+, H
NMR (significant signals, 400 MHz, acetone-d6) d 8.34 (t, 2H, NH),
7.98 (s, 2H, Htriazole), 4.87 (s, 2H, H-1); 13C NMR (significant signals,
1
100 MHz, acetone-d6)
d
166.7 (CONH), 135.6 ðCtqriazoleÞ, 124.2
(CHtriazole), 97.9 (C-1), 69.9 (2C, C-3, C-5), 69.5 (C-2), 67.0
(OCH2), 66.4 (C-4), 62.8 (C-6), 50.1 (OCH2CH2), 36.0 (NCH2).
20
27. Perez-Balderas, F.; Ortega-Munoz, M.; Morales-Sanfrutos, J.; Her-
nandez-Mateo, F.; Calvo-Flores, F. G.; Calvo-Asin, J. A.; Isac-
Garcia, J.; Santoyo-Gonzales, F. Org. Lett. 2003, 5, 1951–1954.
28. In a typical example, 1b (288 mg, 1.2 mmol) and 2b (1008 mg,
2.4 mmol) are dissolved in DME (10 mL), DIPEA (1.24 mL,
7.2 mmol) is added, and the clear solution is stirred at rt (EtO)3PCuI
(ca. 0.1 mmol) is added and stirring at rt is continued until TLC
(toluene/acetone 1:3) indicates complete disappearance of the educts
(14 h). The mixture is concentrated and the residue is chromato-
graphed on silica gel (toluene/acetone 1:3) to give 4b, (980 mg, 76%).
Compound 5c: ½aꢁD +27.9 (c 1.0, CHCl3), EI-MS: 1076.2 [MH]+, 1H
NMR (significant signals, 400 MHz, acetone-d6) d 9.29 (t, 2H, NH),
7.96 (s, 2H, Htriazole), 4.89 (s, 2H, H-1); 13C NMR (significant signals,
100 MHz, acetone-d6)
d
164.1 (CONH), 146.0 ðCtqriazoleÞ, 124.2
(CHtriazole), 98.0 (C-1), 69.9 (C-3), 69.8 (C-5), 69.6 (C-2), 66.9
(OCH2), 66.4 (C-4), 62.9 (C-6), 50.2 (OCH2CH2), 35.4 (NCH2).
29. In a typical example, 4b (540 mg, 0.5 mmol) was dissolved in 7 M
methanolic NH3 solution (10 mL), and the mixture was stirred at rt
for 16 h, whereupon a light blue solution was formed. The solution
was concentrated, and the residue was filtered with CHCl3/MeOH
(1:3) through a short column packed with silica gel to furnish
deacetylated 4b (270 mg, 72%). EI-MS: 739.2 [MH]+.
20
½aꢁD ꢀ13.4 (c 1.0, CHCl3), EI-MS: 1075.3 [MH]+, 1H NMR
(significant signals, 400 MHz, acetone-d6) d 8.33 (t, 2H, NH), 7.86
(s, 2H, Htriazole), 4.80 (d, 2H, H-1, J = 8.1 Hz); 13C NMR (significant
signals, 100 MHz, acetone-d6) d 169.7 (CONH), 135.7 ðCtqriazoleÞ, 124.2
(CHtriazole), 101.0 (C-1), 73.3 (C-3), 72.5 (C-5), 71.9 (C-2), 69.3
(OCH2), 68.4 (C-4), 62.6 (C-6), 50.5 (OCH2CH2), 36.1 (NCH2).
30. Suijkerbuijk, B. M. J. M.; Aerts, B. N. H.; Dijkstra, H. P.; Lutz, M.;
Spek, A. L.; van Koten, G.; Gebbink, R. J. M. K. J. Chem. Soc.,
Dalton Trans. 2007, 1273–1276.
31. Li, Y.; Huffman, J. C.; Flood, A. H. Chem. Commun. 2007, 2692–
2694.
20
Similarly prepared are: Compound 3a: ½aꢁD ꢀ32.6 (c 1.0, DMSO), EI-
MS: 987.3 [MH]+, 1H NMR (significant signals, 400 MHz, DMSO-
d6) d 8.33 (t, 2H, NH), 8.33 (s, 2H, Htriazole), 6.34 (d, 2H, H-1,
J = 9.1 Hz); 13C NMR (significant signals, 100 MHz, DMSO-d6) d
168.2 (CONH), 136.0 ðCtqriazoleÞ, 122.1 (CHtriazole), 83.7 (C-1), 73.2
(C-5), 72.2 (C-2), 70.1 (C-3), 67.5 (C-4), 61.8 (C-6), 34.7 (NCH2).
32. A solution of 4b (100 mg, 93 lmol) and ZnCl2 (12.7 mg, 93 lmol) in
acetone–MeOH (1:3, 5 mL) was stirred at rt for 72 h. Slow removal of
the solvent in a weak vacuum afforded 8a (110 mg, 100%) as a white
20
amorphous solid. ½aꢁD ꢀ15.1 (c 1.0, CHCl3), EI-MS: 1175.2 [MꢀCl]+,
1H NMR (significant signals, 400 MHz, acetone-d6) d 8.69 (s, 2H,
NH), 8.20 (s, 2H, Htriazole), 4.81 (d, 2H, H-1, J = 8.0 Hz); 13C NMR
(significant signals, 100 MHz, acetone-d6) d 167.2 (CONH), 134.6
ðCqtriazoleÞ, 126.1 (CHtriazole), 100.7 (C-1), 72.9 (C-3), 72.1 (C-5), 71.5
(C-2), 68.9 (OCH2), 67.4 (C-4), 62.2 (C-6), 51.6 (OCH2CH2), 34.8
(NCH2).
20
Compound 3b: ½aꢁD ꢀ44.1 (c 1.0, DMSO), EI-MS: 987.3 [MH]+, 1H
NMR (significant signals, 400 MHz, DMSO-d6) d 9.17 (t, 2H, NH),
8.28 (s, 2H, Htriazole), 6.32 (d, 2H, H-1, J = 9.4 Hz); 13C NMR
(significant signals, 100 MHz, DMSO-d6) d 165.7 (CONH), 134.3
ðCqtriazoleÞ, 122.0 (CHtriazole), 83.8 (C-1), 73.3 (C-5), 72.3 (C-2), 70.1